Culturing of cells, especially endothelial cells, with the goal of growing artificial organs is an important development in implantology. One particular advantage of this technology is that implants prepared in this manner are expected to exhibit complete compatibility with the body. Because cell collections cultured ex vivo initially do not have either the shape or the mechanical stability desired for the later implants such as organs, arteries, and the like, such implants can be initially preformed on a form-building or “forming” substrate on which cells are cultured. These form-building substrates can serve as primary supporting structures or supporting substrates on which cells are cultured and developed.
Examples of form-building substrates that have been studied as possible primary supporting structures for such implant formation include polylactides, polyethylene glycols, polyurethanes, polytetrafluoroethylene (PTFE or Teflon®), and inorganic substrates, as well as more common materials such as polyurethanes, polyethylenes, and polypropylenes. Other potential materials included hydrolyzed polyacrylonitrile, hydrophilic polyethers, diacrylates, an expandable shell of epsilon-PTFE, and various hydrogels. This group of potentially applicable materials can also be supplemented by polyvinylpyrrolidone (PVP), polyvinyl alcohols (PVA), polyethylene oxide (PEO), and polyhydroxyethyl methacrylate p(HEMA). Examples of form-building substrates which are supporting structures for cell cultures have been disclosed, for example, in WO 98/56312, WO 96/00103, EP-A-0 810 845, U.S. Pat. Nos. 4,883,699, 4,911,691, 4,480,642, 4,798,876, 4,424,395, and EP-A-0 804 909, the entire disclosures of which are incorporated herein by reference.
Because the inherent properties of these materials are unique, each of these potential substrates exhibits characteristics that make them more or less useful for certain applications in the culture of artificial implants. Similarly, these materials also have certain undesirable properties, such as limited blood or tissue compatibility, difficulty in preparing or processing the material, difficulty in fabricating the supporting substrate itself excessive porosity that leads to strong cell adhesion and results in damage when separating the cultured cell material from the supporting substrate. Other materials may require the addition of plasticizers to achieve the desired properties, which can reduce compatibility with the blood and various cells and tissues.
Accordingly, there is a need to develop substrate materials that can serve as form-building or “forming” substrates, on which cells can be cultured. There is also a need to understand and develop substrate materials as matrices for producing biological materials that can be implanted in a mammal. There is also a need to be able to control the degree or extent of cellular adhesion at or on a substrate, for example within, around, and at the interfacial boundary contacting an implant.